The present invention relates to fumaric acid derivatives and ophthalmic lenses using them. More specifically, the present invention relates to a fumaric acid derivative having a hydrophilic group and a silicon-containing alkyl group within a molecule, and to contact lenses or intraocular lenses using the same.
In the field of medical materials, particularly for ophthalmic lenses, such as contact and intraocular lenses, a variety of monomers have been investigated for use as such materials. Among them, fumaric acid esters, which exhibit advantageous properties, including transparency, mechanical strength and oxygen permeability, when they are processed into lenses, have conventionally been proposed more often than other materials. These properties are considered indispensable for the materials for ophthalmic lenses, because such lenses are applied in direct contact with the living body.
Fumaric acid is a white crystalline powder and has a wide range of industrial applications, including food additives, materials for pharmaceutical products and bath agents. In its chemical structure, two carboxyl groups are located on the both ends of an unsaturated bond of hydrocarbon group. It has been studied as fumaric acid ester contact lens material monomers by introducing a variety of substituents into the carboxyl groups through an ester bond. For example, dialkyl fumarates having a hydrophobic alkyl group, such as linear or branched alkyl or cycloalkyl, as a substituent are disclosed, for example, in JP 02-50450B, JP 06-85030B, and JP 08-23630B, and those having an hydrophilic substituent, such as a phosphorylcholine or hydroxyalkyl group, are disclosed, for example, in Japanese Patent Nos. 3240696, 3227811 and 3612349. Di-(silicon-containing alkyl)fumarates are disclosed, for example, in JP 06-77115B, Japanese Patent Nos. 3050586 and 3453224. Di-(fluoroalkyl)fumarates are disclosed in Japanese Patent No. 3050586.
The above-mentioned fumarates are all of a so-called symmetrical type, in which the substituents are basically identical. This type of fumarates is synthesized primarily for the purpose of improving the oxygen permeability and, in fact, they exhibit superior properties. On the other hand, as partially disclosed in the foregoing patent publications, asymmetrical types of fumarates, in which the substituents are different from each other, have also been investigated. For example, fumarates having silicon-containing alkyl and fluoroalkyl groups (JP 06-25832B, etc.), those having a linear, branched or cyclic alkyl group and a polyoxyethylene chain (JP 04-335007A, etc.), and those having an alkyl group with 1-20 carbon atoms and phosphorylcholine (WO 97/08177) have been used for contact lenses.
These fumarates have been developed for the purpose not only of enhancing the required oxygen supply to the cornea, but also of possessing moderate wettability, transparency as an optical material, biocompatibility and resistance to deposits.
Meanwhile, despite their ability to provide lens materials with good oxygen permeability, the fumaric acid esters proposed in the foregoing patent publications remain minor in the market at present, compared to the lens materials using silicon-containing methacrylates or polydimethylsiloxane macromers. In the field of contact lenses, there are oxygen permeable hard lenses, water-containing soft contact lenses, and silicone hydrogel contact lenses, which recently became commercially available. For oxygen permeable hard lenses and silicone hydrogel contact lenses, silicon-containing methacrylates or macromers as mentioned above are used, and acrylamide monomers, N-vinyl lactams, 2-hydroxymethyl methacrylates, methacrylic acid, and such are used for water-containing soft contact lenses.
One of the reasons why lenses actually employing fumaric acid esters are difficult to make commercially viable is that while the material cost of using a fumaric acid ester alone is high, there is a problem of compatibility between monomers if the fumaric acid ester is used in combination with other general-purpose monomers, although such specifying the reason is not necessarily proper. Specifically, use of a large amount of a fumaric acid ester having a silicon-containing alkyl group as a substituent is desirable on one hand for improving the oxygen permeability, and on the other hand, copolymerization of hydrophilic monomers is required for ensuring moderate wettability of the lens materials. However, since silicon-containing alkyl fumarates generally have poor compatibility with hydrophilic monomers, their use is restricted to a limited composition ratio. Furthermore, when obtaining water-containing soft contact lenses, there often occur problems, such as, in particular, white turbidity after hydration, due to the difficulty in obtaining homogenous polymers because of the difference in polymerization reactivity between monomers used in combination, in addition to the intrinsic problem in their compatibility.
In view of the prior art described above, the inventors have made the present invention. Objectives of the present invention are to provide novel fumaric acid derivatives that may improve the compatibility with other monomers used in combination, in particular, hydrophilic monomers, by taking advantage of the superior features of the fumaric acid derivative monomers, including transparency, mechanical strength and oxygen permeability, and to provide ophthalmic lenses, such as contact lenses or intraocular lenses, using such derivatives.